Organic chemical analysis is a key part of the identification, development, and quality assurance of new pharmaceuticals. For example analytical methods play a critical role in supporting the scaling up of the synthetic route; development of the manufacture of the final dosage form; assessment of stability; and control of quality and consistency of the commercial product.
One of the problems with existing techniques used for the analysis of chemical substances is the speed and quality of decision-making. There is a need for products and processes to be characterised more quickly and more fully, with the ultimate aim of decreasing development times, reducing manufacturing costs, and increasing the quality and safety of the final product.
Another problem is that most pharmaceuticals are marketed as solid dosage forms, for example oral tablets, but the majority of the organic chemical analysis techniques used are solution based. Some examples of analytical techniques of this nature that are widely used in assessing the quantity of active agent, chemical purity, and the identification of both active agent and impurities are HPLC (high pressure liquid chromatography), electro-spray MS (mass spectrometry), and solution NMR (nuclear magnetic resonance). Whilst such techniques enable tight control of the quality and consistency of the dosage form of a pharmaceutical, they inevitably require time and effort in sample preparation and are inherently destructive in nature.
Other important information, such as the polymorphic form of the active agent, is lost by solution-based methods and so solid-state techniques are required to be used in an attempt to attain such information. Examples of some solid-state analytical techniques that have been developed include IR (infra-red), powder XRD (x-ray diffraction), and solid state NMR. Problems with these techniques, however, include:                they are performed off-line;        they require the sample to be removed from any packaging;        they are slow, time intensive, expensive techniques—some NMR analyses can take 24 hours;        near IR techniques require a significant calibration step;        a NMR requires a large bulky magnet which can be dangerous if it has a high field strength, because metallic objects can be launched by its magnetic field;        NMR spectra are difficult to interpret because of many overlapping lines;        NMR & XRD are generally very expensive machines.        
The problem with off-line pharmaceutical analysis is that it is usually conducted remotely of the process sought to be controlled by the results of the analysis. Most control strategies rely on end point testing in which the manufactured material is sampled and the samples brought to the laboratory for testing. End point testing imposes limits on the timescale in which process changes can be made.
Techniques such as Near IR (NIR) have evolved that provide for in-line testing, but as NIR is a secondary technique, a significant calibration exercise is required before data can be interpreted in a meaningful way.
NQR is a technique in radiofrequency (RF) spectroscopy in which the signals arise from the interaction of the electric quadrupole moment of the quadrupolar nuclei in the sample with the electric field gradient (EFG) of their surroundings. RF radiation excites transitions between the energy levels generated by this interaction at frequencies, which are characteristic of a given material.
Some of the characteristics of NQR are that the method of its deployment is generally non-invasive and that NQR signals are only seen in solids, but suspensions of solid materials within liquids are eligible for detection. Furthermore, it is relatively inexpensive to deploy. Unlike NMR, for example, no static magnetic field is necessary, so remote materials and large volumes—at the moment, the record is 8000 litres2—can be examined.
NQR has been mooted for many years as a technique that can be used for the detection of explosives and narcotics in the field, as opposed to the laboratory. Most of these substances contain quadrupolar nuclei such as nitrogen-14 (14N) nuclei, the spectral lines of which are usually located at low frequencies where NQR signals detected have low intensity. In this application of NQR, specimens are sampled to ascertain the threshold presence of a targeted chemical substance indicating the presence of a particular type of explosive or narcotic.
A number of problems associated with deploying NQR in the field as a reliable and quick technique to ascertain the presence of the targeted substance have arisen, however, preventing the technique from being used more widely than it has to date. Some of these problems include what are known as intensity variations, where the amplitude of the resultant NQR signal strongly depends on the frequency offset and repetition time of the exciting RF radiation, and the effect of temperature on changing the frequency at which an NQR signal may be detected.
Notwithstanding these problems, processes have been developed in more recent times to overcome these problems, making NQR more reliable as a technique for detecting the presence of a substance. Moreover, it is the realisation that new developments in pulsed RF spectroscopy and new methods of improving the signal-to-noise ratio (SNR) now suggest the possibility of a much wider application of NQR techniques to chemical analysis, particularly at the low radiofrequencies typical of 14N, which was not previously the case.